How to check whether a blood pressure monitor has been properly validated for accuracy

Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non‐validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non‐validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country‐specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross‐checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors.     

Acetylcholinesterase in the rat neurohypophysis is decreased after dehydration and released by stimulation of the pituitary stalk

Specific acetylcholinesterase and non-specific cholinesterases are present in all three lobes of the rat pituitary gland. This paper describes two new observations on hypophyseal acetylcholinesterase. Firstly, a prolonged increase of neurohormone secretion evoked by dehydration and sodium loading was accompanied by a decrease in the acetylcholinesterase activity localized to the neural lobe, where acetylcholinesterase has previously been demonstrated in fine nerve fibres. Secondly, electrical stimulation of the pituitary stalk in vitro elicited the release of acetylcholinesterase and non-specific cholinesterases from the combined neural and intermediate lobe indicating that the enzyme can be released from nerve endings in the hypophysis by action potentials. The observed loss of enzyme activity during dehydration may be the consequence of a prolonged activation of cholinergic nerves in the gland, leading to an increased release of acetylcholinesterase, which is not immediately replaced by fresh enzyme. The decrease in acetylcholinesterase in the neural lobe during dehydration may also be connected with its peptidase function and thus with the previously observed loss of substance P from the neural lobe during dehydration [Holzbauer et al. (1984) Neurosci. Lett. 47, 23-28].     

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune-related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.     

Cigarette smoking and trisomy 21 at amniocentesis

Several studies raise the possibility that smoking during pregnancy is associated with a slightly decreased odds of trisomy 21 at birth. If it is, associations may reflect decreased incidence at conception, increased intrauterine loss (at one or several times in gestation), or both. Women ( n = 13,729) undergoing prenatal diagnosis completed a questionnaire before learning karyotype results. For each women with a trisomy, up to 4 controls with chromosomally normal pregnancies, matched for age and hospital, were selected. Analyses drew on the 89 trisomy 21-control matched m-tuples in which diagnosis was by amniocentesis at 14-26 weeks. We compared the odds of smoking at last menstrual period and in the past in cases and controls. The odds of current smoking versus never smoking were decreased [adjusted odds ratio = 0.8, 95% confidence interval (CI) 0.4-1.6]; and the odds of exsmoking increased (adjusted odds ratio = 1.4, 95% CI 0.9-2.4) in trisomy 21 cases. The association with current smoking was essentially unchanged when the unexposed reference group was defined as exsmokers and women who never smoked (adjusted odds ratio = 0.7, 95% CI 0.4-1.4). These results for current smoking agree well with a summary estimate based on combined studies of births. One interpretation is that at amniocentesis, as has been reported for births, current smoking is associated with a slightly decreased odds of trisomy 21. If associations at amniocentesis and birth are of equal magnitude, the explanation that observations at birth reflect increased loss in the second half of pregnancy with current smoking is unlikely to be correct. However, the present amniocentesis evidence supports this interpretation weakly and is insufficient to rule out the null hypothesis that smoking is unrelated to trisomy 21. © 1993 Wiley-Liss. Inc.     

Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management.

The dangers of phaeochromocytomas are mainly due to the capability of these neuroendocrine tumours to secrete large quantities of vasoactive catecholamines, thereby increasing blood pressure and causing other related adverse events or complications. Phaeochromocytomas are often missed, sometimes only becoming apparent during therapeutic interventions that provoke release or interfere with the disposition of catecholamines produced by the tumours. Because phaeochromocytomas are rare, evidence contraindicating use of specific drugs is largely anecdotal or based on case reports. The heterogeneous nature of the tumours also makes adverse reactions highly variable among patients. Some drugs, such as dopamine D(2) receptor antagonists (e.g. metoclopramide, veralipride) and beta-adrenergic receptor antagonists (beta-blockers) clearly carry high potential for adverse reactions, while others such as tricyclic antidepressants seem more inconsistent in producing complications. Other drugs capable of causing adverse reactions include monoamine oxidase inhibitors, sympathomimetics (e.g. ephedrine) and certain peptide and corticosteroid hormones (e.g. corticotropin, glucagon and glucocorticoids). Risks associated with contraindicated medications are easily minimised by adoption of appropriate safeguards (e.g. adrenoceptor blockade). Without such precautions, the state of cardiovascular vulnerability makes some drugs and manipulations employed during surgical anaesthesia particularly dangerous. Problems arise most often when drugs or therapeutic procedures are employed in patients in whom the tumour is not suspected. In such cases, it is extremely important for the clinician to recognise the possibility of an underlying catecholamine-producing tumour and to take the most appropriate steps to manage and treat adverse events and clinical complications.